Advanced search
Publication Cover
Expert Opinion on Therapeutic Targets Volume 12, 2008 - Issue 7
Submit an article Journal homepage
247
Views
16
CrossRef citations to date
0
Altmetric
Review

Molecular targeting of E3 ligases – a therapeutic approach for cancer

Manikandan Lakshmanan Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
,
Usha Bughani Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
,
Senthil Duraisamy Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
,
Manish Diwan Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
,
Sunanda Dastidar Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
&
Abhijit Ray Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India +91 124 2342001 10, ext. 5348; +91 124 2343544; [email protected]
Pages 855-870 | Published online: 13 Jun 2008

Bibliography

  • Deshaies RJ. SCF and Cullin/Ring H2-based ubiquitin ligases. Ann Rev Cell Dev Biol 1999;15:435-67
  • Hershko A, Ciechanover A. The ubiquitin system. Ann Rev Biochem 1998;67:425-79
  • Pickart CM. Mechanisms underlying ubiquitination. Ann Rev Biochem 2001;70:503-33
  • Nandi D, Tahiliani P, Kumar A, et al. The ubiquitin-proteasome system. J Biosci 2006;31:137-55
  • Myung J, Kim KB, Crews CM. The ubiquitin-proteasome pathway and proteasome inhibitors. Med Res Rev 2001;21:245-73
  • Robinson PA, Ardley HC. Ubiquitin-protein ligases–novel therapeutic targets? Curr Protein Pept Sci 2004;5:163-76
  • Sun Y. E3 ubiquitin ligases as cancer targets and biomarkers. Neoplasia 2006;8:645-54
  • Freemont PS. RING for destruction? Curr Biol 2000;10:R84-7
  • Fang S, Lorick KL, Jensen JP, et al. RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis and for molecular targets in cancer. Semin Cancer Biol 2003;13:5-14
  • Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 2005;6:9-20
  • Scheffner M, Nuber U, Huibregtse JM. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 1995;373:81-3
  • Schwarz SE, Rosa JL, Scheffner M. Characterization of human hect domain family members and their interaction with UbcH5 and UbcH7. J Biol Chem 1998;273:12148-54
  • Deveraux QL, Reed JC. IAP family proteins–suppressors of apoptosis. Genes Dev 1999;13:239-52
  • Salvesen GS, Duckett CS. IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol 2002;3:401-10
  • Hofmann K, Bucher P, Tschopp J. The CARD domain: a new apoptotic signalling motif. Trends Biochem Sci 1997;22:155-6
  • Fong WG, Liston P, Rajcan-Separovic E, et al. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics 2000;70:113-22
  • Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 2000;6:1796-803
  • Wu M, Yuan S, Szporn AH, et al. Immunocytochemical detection of XIAP in body cavity effusions and washes. Mod Pathol 2005;18:1618-22
  • Ramaswamy S, Tamayo P, Rifkin R, et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 2001;98:15149-54
  • Lacasse EC, Kandimalla ER, Winocour P, et al. Application of XIAP antisense to cancer and other proliferative disorders: development of AEG35156/ GEM640. Ann NY Acad Sci 2005;1058:215-34
  • LaCasse EC, Cherton-Horvat GG, Hewitt KE, et al. Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis. Clin Cancer Res 2006;12:5231-41
  • Wu TY, Wagner KW, Bursulaya B, et al. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction. Chem Biol 2003;10:759-67
  • Carter BZ, Gronda M, Wang Z, et al. Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 2005;105:4043-50
  • Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004;5:25-35
  • Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site. J Med Chem 2004;47:4147-50
  • Oost TK, Sun C, Armstrong RC, et al. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem 2004;47:4417-26
  • Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design of potent, conformationally constrained Smac mimetics. J Am Chem Soc 2004;126:16686-7
  • Fulda S, Wick W, Weller M, et al. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med 2002;8:808-15
  • Sun H, Nikolovska-Coleska Z, Lu J, et al. Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic. J Med Chem 2006;49:7916-20
  • Zobel K, Wang L, Varfolomeev E, et al. Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs. ACS Chem Biol 2006;1:525-33
  • Nikolovska-Coleska Z, Xu L, Hu Z, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 2004;47:2430-40
  • Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature 2000;408:307-10
  • Fakharzadeh SS, Rosenblum-Vos L, Murphy M, et al. Structure and organization of amplified DNA on double minutes containing the mdm2 oncogene. Genomics 1993;15:283-90
  • Haupt Y, Maya R, Kazaz A, et al. Mdm2 promotes the rapid degradation of p53. Nature 1997;387:296-9
  • Momand J, Zambetti GP, Olson DC, et al. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992;69:1237-45
  • Fang S, Jensen JP, Ludwig RL, et al. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 2000;275:8945-51
  • Honda R, Yasuda H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene 2000;19:1473-6
  • Oliner JD, Kinzler KW, Meltzer PS, et al. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992;358:80-3
  • Momand J, Jung D, Wilczynski S, et al. The MDM2 gene amplification database. Nucleic Acids Res 1998;26:3453-9
  • Yang Y, Ludwig RL, Jensen JP, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 2005;7:547-59
  • Klein C, Vassilev LT. Targeting the p53-MDM2 interaction to treat cancer. Br J Cancer 2004;91:1415-9
  • Tovar C, Rosinski J, Filipovic Z, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci USA 2006;103:1888-93
  • Grasberger BL, Lu T, Schubert C, et al. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem 2005;48:909-12
  • Koblish HK, Zhao S, Franks CF, et al. Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo. Mol Cancer Ther 2006;5:160-9
  • Leonard K, Marugan JJ, Raboisson P, et al. Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity. Bioorg Med Chem Lett 2006;16:3463-8
  • Parks DJ, LaFrance LV, Calvo RR, et al. Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein-protein interaction through structure-based drug design. Bioorg Med Chem Lett 2006;16:3310-4
  • Ding K, Lu Y, Nikolovska-Coleska Z, et al. Structure-based design of potent non-peptide MDM2 inhibitors. J Am Chem Soc 2005;127:10130-1
  • Ding K, Lu Y, Nikolovska-Coleska Z, et al. Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem 2006;49:3432-5
  • Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004;10:1321-8
  • Krajewski M, Ozdowy P, D'Silva L, et al. NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro. Nat Med 2005;11:1135-6; author reply 36-7
  • Neumann HP, Lips CJ, Hsia YE, et al. Von Hippel-Lindau syndrome. Brain Pathol 1995;5:181-93
  • Shiao YH. The von Hippel-Lindau gene and protein in tumorigenesis and angiogenesis: a potential target for therapeutic designs. Curr Med Chem 2003;10:2461-70
  • Ivan M, Kondo K, Yang H, et al. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 2001;292:464-8
  • Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001;292:468-72
  • Salnikow K, Donald SP, Bruick RK, et al. Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J Biol Chem 2004;279:40337-44
  • Kim MS, Kwon HJ, Lee YM, et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 2001;7:437-43
  • Jones MK, Szabo IL, Kawanaka H, et al. von Hippel Lindau tumor suppressor and HIF-1α: new targets of NSAIDs inhibition of hypoxia-induced angiogenesis. FASEB J 2002;16:264-6
  • Sweeney C, Carraway KL 3rd. Negative regulation of ErbB family receptor tyrosine kinases. Br J Cancer 2004;90:289-93
  • Thien CB, Blystad FD, Zhan Y, et al. Loss of c-Cbl RING finger function results in high-intensity TCR signaling and thymic deletion. EMBO J 2005;24:3807-19
  • Levkowitz G, Waterman H, Ettenberg SA, et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell 1999;4:1029-40
  • Mosesson Y, Shtiegman K, Katz M, et al. Endocytosis of receptor tyrosine kinases is driven by monoubiquitylation, not polyubiquitylation. J Biol Chem 2003;278:21323-6
  • Duan L, Miura Y, Dimri M, et al. Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth factor receptor but is dispensable for endocytosis. J Biol Chem 2003;278:28950-60
  • Klapper LN, Waterman H, Sela M, et al. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res 2000;60:3384-8
  • Miyake S, Mullane-Robinson KP, Lill NL, et al. Cbl-mediated negative regulation of platelet-derived growth factor receptor-dependent cell proliferation. A critical role for Cbl tyrosine kinase-binding domain. J Biol Chem 1999;274:16619-28
  • Taher TE, Tjin EP, Beuling EA, et al. c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination. J Immunol 2002;169:3793-800
  • Takeuchi H, Kim J, Fujimoto A, et al. X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. Clin Cancer Res 2005;11:7621-8
  • Zeng S, Xu Z, Lipkowitz S, et al. Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl). Blood 2005;105:226-32
  • Duval M, Bedard-Goulet S, Delisle C, et al. Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR involves Cbl-mediated ubiquitination. Consequences on nitric oxide production from endothelial cells. J Biol Chem 2003;278:20091-7
  • Kobayashi S, Sawano A, Nojima Y, et al. The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1). FASEB J 2004;18:929-31
  • Scott RP, Eketjall S, Aineskog H, et al. Distinct turnover of alternatively spliced isoforms of the RET kinase receptor mediated by differential recruitment of the Cbl ubiquitin ligase. J Biol Chem 2005;280:13442-9
  • Wong A, Lamothe B, Lee A, et al. FRS2α attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl. Proc Natl Acad Sci USA 2002;99:6684-9
  • Diamonti AJ, Guy PM, Ivanof C, et al. An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc Natl Acad Sci USA 2002;99:2866-71
  • Qiu XB, Goldberg AL. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc Natl Acad Sci USA 2002;99:14843-8
  • Scully R, Livingston DM. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 2000;408:429-32
  • Brzovic PS, Rajagopal P, Hoyt DW, et al. Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Nat Struct Biol 2001;8:833-7
  • Wu LC, Wang ZW, Tsan JT, et al. Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 1996;14:430-40
  • Brzovic PS, Keeffe JR, Nishikawa H, et al. Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex. Proc Natl Acad Sci USA 2003;100:5646-51
  • Xia Y, Pao GM, Chen HW, et al. Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem 2003;278:5255-63
  • Brzovic PS, Meza JE, King MC, et al. BRCA1 RING domain cancer-predisposing mutations. Structural consequences and effects on protein-protein interactions. J Biol Chem 2001;276:41399-406
  • Hashizume R, Fukuda M, Maeda I, et al. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem 2001;276:14537-40
  • Ruffner H, Joazeiro CA, Hemmati D, et al. Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Proc Natl Acad Sci USA 2001;98:5134-9
  • Chen A, Kleiman FE, Manley JL, et al. Autoubiquitination of the BRCA1-BARD1 RING ubiquitin ligase. J Biol Chem 2002;277:22085-92
  • Nishikawa H, Ooka S, Sato K, et al. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase. J Biol Chem 2004;279:3916-24
  • Wu-Baer F, Lagrazon K, Yuan W, et al. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. J Biol Chem 2003;278:34743-6
  • Mallery DL, Vandenberg CJ, Hiom K. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains. EMBO J 2002;21:6755-62
  • Jensen DE, Proctor M, Marquis ST, et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 1998;16:1097-112
  • Holt JT, Thompson ME, Szabo C, et al. Growth retardation and tumour inhibition by BRCA1. Nat Genet 1996;12:298-302
  • Tait DL, Obermiller PS, Redlin-Frazier S, et al. A phase I trial of retroviral BRCA1sv gene therapy in ovarian cancer. Clin Cancer Res 1997;3:1959-68
  • Tait DL, Obermiller PS, Hatmaker AR, et al. Ovarian cancer BRCA1 gene therapy: Phase I and II trial differences in immune response and vector stability. Clin Cancer Res 1999;5:1708-14
  • Tait DL, Obermiller PS, Holt JT. Preclinical studies of a new generation retroviral vector for ovarian cancer BRCA1 gene therapy. Gynecol Oncol 2000;79:471-6
  • Sun Y, Tan M, Duan H, et al. SAG/ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions. Antioxid Redox Signal 2001;3:635-50
  • Cardozo T, Pagano M. The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 2004;5:739-51
  • Jin J, Cardozo T, Lovering RC, et al. Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 2004;18:2573-80
  • Bornstein G, Bloom J, Sitry-Shevah D, et al. Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem 2003;278:25752-7
  • Kamura T, Hara T, Kotoshiba S, et al. Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proc Natl Acad Sci USA 2003;100:10231-6
  • Tsvetkov LM, Yeh KH, Lee SJ, et al. p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27. Curr Biol 1999;9:661-4
  • Newton K, Vucic D. Ubiquitin ligases in cancer: ushers for degradation. Cancer Invest 2007;25:502-13
  • Latres E, Chiarle R, Schulman BA, et al. Role of the F-box protein Skp2 in lymphomagenesis. Proc Natl Acad Sci USA 2001;98:2515-20
  • Shim EH, Johnson L, Noh HL, et al. Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate. Cancer Res 2003;63:1583-8
  • Yaron A, Hatzubai A, Davis M, et al. Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature 1998;396:590-4
  • Karin M, Cao Y, Greten FR, et al. NF-κB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002;2:301-10
  • Chen Z, Hagler J, Palombella VJ, et al. Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev 1995;9:1586-97
  • Yaron A, Gonen H, Alkalay I, et al. Inhibition of NF-κ-B cellular function via specific targeting of the I-κ-B-ubiquitin ligase. EMBO J 1997;16:6486-94
  • Watanabe N, Arai H, Nishihara Y, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFβ-TrCP. Proc Natl Acad Sci USA 2004;101:4419-24
  • Nakayama KI, Nakayama K. Regulation of the cell cycle by SCF-type ubiquitin ligases. Semin Cell Dev Biol 2005;16:323-33
  • Nakayama KI, Nakayama K. Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 2006;6:369-81
  • Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005;6:635-45
  • Castro A, Bernis C, Vigneron S, et al. The anaphase-promoting complex: a key factor in the regulation of cell cycle. Oncogene 2005;24:314-25
  • Yoon HJ, Feoktistova A, Wolfe BA, et al. Proteomics analysis identifies new components of the fission and budding yeast anaphase-promoting complexes. Curr Biol 2002;12:2048-54
  • Zachariae W, Schwab M, Nasmyth K, et al. Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 1998;282:1721-4
  • Harper JW, Burton JL, Solomon MJ. The anaphase-promoting complex: it's not just for mitosis any more. Genes Dev 2002;16:2179-206
  • Perez LH, Antonio C, Flament S, et al. Xkid chromokinesin is required for the meiosis I to meiosis II transition in Xenopus laevis oocytes. Nat Cell Biol 2002;4:737-42
  • Antonio C, Ferby I, Wilhelm H, et al. Xkid, a chromokinesin required for chromosome alignment on the metaphase plate. Cell 2000;102:425-35
  • Ayad NG, Rankin S, Murakami M, et al. Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Cell 2003;113:101-13
  • Wang Q, Moyret-Lalle C, Couzon F, et al. Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene 2003;22:1486-90
  • Wolf G, Hildenbrand R, Schwar C, et al. Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer. Pathol Res Pract 2000;196:753-9
  • Chen C, Matesic LE. The Nedd4-like family of E3 ubiquitin ligases and cancer. Cancer Metastasis Rev 2007;26:587-604
  • Lin X, Liang M, Feng XH. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem 2000;275:36818-22
  • Fukuchi M, Fukai Y, Masuda N, et al. High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Res 2002;62:7162-5
  • Laine A, Ronai Z. Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. Oncogene 2007;26:1477-83
  • Chen C, Zhou Z, Ross JS, et al. The amplified WWP1 gene is a potential molecular target in breast cancer. Int J Cancer 2007;121:80-7
  • Wang F, Zhu Y, Huang Y, et al. Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis. Oncogene 2005;24:3875-85
  • Wilkinson KD. Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 2000;11:141-8
  • Love KR, Catic A, Schlieker C, et al. Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat Chem Biol 2007;3:697-705
  • Yang JM. Emerging roles of deubiquitinating enzymes in human cancer. Acta Pharmacol Sin 2007;28:1325-30
  • Graner E, Tang D, Rossi S, et al. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 2004;5:253-61
  • Pflug BR, Pecher SM, Brink AW, et al. Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. Prostate 2003;57:245-54
  • Rossi S, Graner E, Febbo P, et al. Fatty acid synthase expression defines distinct molecular signatures in prostate cancer. Mol Cancer Res 2003;1:707-15
  • Priolo C, Tang D, Brahamandan M, et al. The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Res 2006;66:8625-32
  • Cheon KW, Baek KH. HAUSP as a therapeutic target for hematopoietic tumors (review). Int J Oncol 2006;28:1209-15
  • Schoenfeld AR, Apgar S, Dolios G, et al. BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol Cell Biol 2004;24:7444-55
  • Lu Y, Nikolovska-Coleska Z, Fang X, et al. Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy. J Med Chem 2006;49:3759-62

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.